The Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston.
Jacobi is currently in the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.
Arch Pathol Lab Med. 2021 Jan 1;145(1):46-54. doi: 10.5858/arpa.2019-0398-OA.
CONTEXT.—: The approval of pembrolizumab for treatment of patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) advanced cancers has led to increased requests for MSI and/or MMR immunoperoxidase (IPOX) testing. Diagnoses for patients with advanced-stage cancer are frequently made from cytology specimens.
OBJECTIVE.—: To investigate the feasibility of using cell block (CB) preparations of effusions for MMR IPOX evaluation.
DESIGN.—: Surgical pathology cases of colorectal and endometrial carcinomas with known MMR/MSI status and matched effusions with available CBs were identified. Cell block sections were evaluated for adequacy and stained with MMR IPOX (MSH2, MSH6, MLH1, and PMS2). The CBs were reviewed, the number of tumor cells quantified, and MMR IPOX was interpreted as retained, lost, suboptimal, or noncontributory.
RESULTS.—: We identified 748 cases with MMR/MSI testing on surgical specimens having matched effusions. Of these, 131 cases (17.5%) had an available CB and 53 were deemed adequate for MMR IPOX staining. MMR IPOX results between effusion CBs and surgical pathology specimens were concordant in 45 of 53 (85%), inconclusive in 6 of 53 (11%), and discordant in 2 of 53 (4%) cases.
CONCLUSIONS.—: There was high concordance of MMR IPOX testing between cytologic and surgical specimens, with no false-positive and 2 false-negative CB results. Limited tumor cells, staining in cells indefinite as tumor, tumor staining heterogeneity, and lack of internal control staining were problematic in some cases. Our findings indicate that cytologic effusion specimens may be suitable substrates for MMR IPOX biomarker testing; however, inconclusive cases need to be interpreted with caution.
帕博利珠单抗获批用于治疗微卫星高度不稳定（MSI-H）或错配修复缺陷（dMMR）的晚期癌症患者，这导致对 MSI 和/或 MMR 免疫过氧化物酶（IPOX）检测的需求增加。晚期癌症患者的诊断通常来自细胞学标本。
研究使用细胞学标本的细胞块（CB）制备物进行 MMR IPOX 评估的可行性。
鉴定了已知 MMR/MSI 状态的结直肠和子宫内膜癌的外科病理病例，并匹配了具有可用 CB 的渗出液。对 CB 切片进行了充分性评估，并进行了 MMR IPOX（MSH2、MSH6、MLH1 和 PMS2）染色。回顾了 CB，量化了肿瘤细胞数量，并将 MMR IPOX 解释为保留、丢失、不理想或无贡献。
我们鉴定了 748 例具有外科标本 MMR/MSI 检测结果的病例，这些病例有匹配的渗出液。其中，131 例（17.5%）有可用的 CB，53 例被认为适合进行 MMR IPOX 染色。53 例中有 45 例（85%）的 MMR IPOX 结果与外科病理标本一致，53 例中有 6 例（11%）结果不确定，53 例中有 2 例（4%）结果不一致。
细胞学和外科标本的 MMR IPOX 检测具有高度一致性，无假阳性和 2 例假阴性 CB 结果。在一些情况下，肿瘤细胞数量有限、细胞不确定为肿瘤的染色、肿瘤染色异质性以及缺乏内部对照染色是有问题的。我们的发现表明，细胞学渗出液标本可能适合作为 MMR IPOX 生物标志物检测的底物；然而，不确定的病例需要谨慎解释。
